Alemtuzumab Overview

Introduction of Alemtuzumab

Alemtuzumab is a humanized anti-CD52 IgG1 monoclonal antibody that depletes CD52-expressing cells from the circulation. This drug (marketed as Campath, MabCampath or Campath-1H and currently under further development as Lemtrada) is a monoclonal antibody used in the treatment of chronic lymphocytic leukemia (CLL), cutaneous T-cell lymphoma (CTCL) and T-cell lymphoma. It was approved by the US Food and Drug Administration for CLL patients who have been treated with alkylating agents and who have failed fludarabine therapy. Since the approval of the US Food and Drug Administration (FDA) in November 2014, alemtuzumab is approved in over 30 countries for the therapy of relapsing-remitting multiple sclerosis (RRMS). Alemtuzumab demonstrated superiority to subcutaneous (sc) interferon β-1a (IFNβ-1a), an established disease-modifying therapy (DMT) for RRMS. The high efficacy of alemtuzumab, with remarkable effects on clinical and radiological disease outcome parameters is offset by frequent and significant adverse events. Besides infusion-associated reactions (IAR), mild to moderate infections, especially the occurrence of secondary autoimmune disease, has somewhat dampened enthusiasm for alemtuzumab. Approximately 30%-40% of patients develop secondary autoimmune diseases predominantly affecting thyroid, kidney and thrombocytic function.

Mechanism of Action of Alemtuzumab

CD52 is a 21-28 kDa cell surface glycoprotein attached to the cell membrane by a glycosylphosphatidyl-inositol anchor of 12 amino acids. CD52 is one of the most abundant membrane glycoproteins on T and B lymphocytes and is also expressed on natural killer (NK) cells, monocytes, macrophages, dendritic cells, and eosinophilic granulocytes and to a lesser extent on neutrophilic granulocytes. CD52 is not expressed on erythrocytes, platelets, and hematopoietic progenitor cells. The exact function of CD52 is unknown but it is suggested that the molecule may be involved in T lymphocyte co-stimulation, the induction of regulatory T lymphocytes, and T lymphocyte migration and adhesion. Alemtuzumab is an IgG1 kappa with human variable framework and constant regions, and complementarity-determining regions derived from a rat monoclonal antibody. This agent selectively binds to CD52, thereby triggering a host immune response that results in lysis of CD52⁺ cells. In other words, alemtuzumab induces antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), and activates pro-apoptotic pathways on CD52-expressing cells. Administration of alemtuzumab causes a profound depletion of T and B lymphocytes, NK cells, dendritic cells, granulocytes, and monocytes by three mechanisms: complement-dependent cytotoxicity (through C1q activation and subsequent generation of the membrane attack complex), antibody-dependent cellular cytotoxicity (after the activation of NK cells and macrophages through their IgG fragment C receptor), and induction of apoptosis. Depletion of peripheral lymphocytes occurs within 1h after alemtuzumab administration. Lymphocyte depletion from secondary lymphoid tissues occurs over 3-5 days. Alemtuzumab administration significantly depletes peripheral monocytes and NK cells.

Fig 1. Mechanism of Action of Alemtuzumab

Table 1. Clinical Projects of Alemtuzumab*

Table 2. Approved Drugs of Alemtuzumab**

INN (trade name)	Therapeutic area	Dose	Strength	Route	Company	Marketing start	Market
Compath	B-cell chronic lymphocytic leukemia	VIAL	10MG/ML	Intravenous	Genzyme	June 23, 2000
Lemtrada	Relapsing forms of multiple sclerosis (MS)	Injection	12MG/1.2ML	Intravenous infusion	Genzyme	September 17, 2017

What We Provide

Therapeutic Antibody

We provide high-quality (IgG1 - kappa type) for use in FuncS, IF, Neut, ELISA, FC, IP, ICC and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

Reference
*The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?term=Alemtuzumab

**Information presented in the table were collected from the following website:
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=103948